The long-acting Ca2+-channel blocker azelnidipine prevents left ventricular remodeling after myocardial infarction.

Long-acting Ca(2+)-channel blockers have been reported to be effective in treating ischemic heart disease. However, their effects on cardiac remodeling after myocardial infarction (MI) are still unclear. We performed this study to examine the effect of azelnidipine on left ventricular (LV) remodeling, including systolic and diastolic dysfunction, in rats with MI. MI was induced by ligation of the left anterior descending artery. The rats were then separated into 3 groups: a sham-operated group (n = 9), untreated MI group (n = 10), and azelnidipine-treated MI group (n = 10). Four weeks after MI, hemodynamic measurements and Doppler echocardiographic assessment were performed. LV weight and LV end-diastolic dimension were significantly higher in the untreated MI group than in the sham-operated group. Azelnidipine significantly prevented the increases in these parameters. Azelnidipine also improved the ejection fraction (42 +/- 3%, P<0.05) and the E wave to A wave ratio (3.2 +/- 0.5, P<0.05), compared with the untreated MI group (31 +/- 3% and 5.3 +/- 0.8, respectively). In conclusion, azelnidipine can prevent LV remodeling and improve systolic and diastolic function after MI. Administration of long-acting Ca(2+)-channel blockers after MI is an effective strategy for treating MI.

[1]  K. Sunagawa,et al.  Long-Acting Calcium Channel Blocker, Azelnidipine, Increases Endothelial Nitric Oxide Synthase in the Brain and Inhibits Sympathetic Nerve Activity , 2007, Clinical and experimental hypertension.

[2]  A. Nishiyama,et al.  Effects of a New Calcium Channel Blocker, Azelnidipine, on Systemic Hemodynamics and Renal Sympathetic Nerve Activity in Spontaneously Hypertensive Rats , 2005, Hypertension Research.

[3]  Takahiro Shimizu,et al.  Calcium Channel Blockades Exhibit Anti-Inflammatory and Antioxidative Effects by Augmentation of Endothelial Nitric Oxide Synthase and the Inhibition of Angiotensin Converting Enzyme in the NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Rat Aorta: Vasoprotective Effects beyond the Blood Press , 2005, Hypertension Research.

[4]  Lie Gao,et al.  Superoxide Mediates Sympathoexcitation in Heart Failure: Roles of Angiotensin II and NAD(P)H Oxidase , 2004, Circulation research.

[5]  T. Imaizumi,et al.  Azelnidipine, A Newly Developed Long-Acting Calcium Antagonist, Inhibits Tumor Necrosis Factor-&agr;-Induced Interleukin-8 Expression in Endothelial Cells through its Anti-Oxidative Properties , 2004, Journal of cardiovascular pharmacology.

[6]  M. Kohno,et al.  Antioxidant Effect of a New Calcium Antagonist, Azelnidipine, in Cultured Human Arterial Endothelial Cells , 2004, The Journal of international medical research.

[7]  A. Takeshita,et al.  Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction , 2002, Circulation.

[8]  D. Sawyer,et al.  Adrenergic regulation of cardiac myocyte apoptosis , 2001, Journal of cellular physiology.

[9]  N. Kobayashi,et al.  Celiprolol stimulates endothelial nitric oxide synthase expression and improves myocardial remodeling in deoxycorticosterone acetate-salt hypertensive rats , 2001, Journal of hypertension.

[10]  Hiroyuki Tsutsui,et al.  Treatment With Dimethylthiourea Prevents Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction in Mice: Role of Oxidative Stress , 2000, Circulation research.

[11]  P. Carmeliet,et al.  Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction. , 2000, The American journal of pathology.

[12]  A. Takeshita,et al.  Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. , 2000, Circulation research.

[13]  Shokei Kim,et al.  Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography. , 1999, Hypertension.

[14]  I. Dixon,et al.  Expression of Gqα and PLC-β in Scar and Border Tissue in Heart Failure Due to Myocardial Infarction , 1998 .

[15]  Shokei Kim,et al.  Long acting calcium antagonist amlodipine prevents left ventricular remodeling after myocardial infarction in rats. , 1998, Cardiovascular research.

[16]  M. Alderman,et al.  Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients , 1997, The Lancet.

[17]  B. Psaty,et al.  Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. , 1995, Circulation.

[18]  T. Raghunathan,et al.  The risk of myocardial infarction associated with antihypertensive drug therapies. , 1995, JAMA.

[19]  Y. Yagil,et al.  Azelnidipine (CS‐905), A Novel Dihydropyridine Calcium Channel Blocker with Gradual Onset and Prolonged Duration of Action , 1995 .

[20]  Shokei Kim,et al.  Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats. , 1993, Journal of molecular and cellular cardiology.

[21]  R B D'Agostino,et al.  Influence of heart rate on mortality among persons with hypertension: the Framingham Study. , 1993, American heart journal.

[22]  M. Pfeffer,et al.  Ventricular Remodeling After Myocardial Infarction: Experimental Observations and Clinical Implications , 1990, Circulation.

[23]  I. Kuwajima.  Pharmacokinetic study of CS-905 (azelnidipine) in elderly patients with essential hypertension , 2000 .

[24]  K. Kobayashi.  Long-term effects of CS-905 (azelnidipine) on diurnal blood pressure variation and hemodynamics in patients with essential hypertension , 2000 .

[25]  H. Nishino,et al.  Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker. , 1989, Japanese journal of pharmacology.